Enhanced Expression of Interferon-regulated Genes in the Liver of Patients with Chronic Hepatitis C Virus Infection: Detection by Suppression-subtractive Hybridization

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2001 Jan 11

PMID 11152506

Citations 32

Authors

R Patzwahl

V Meier

G Ramadori

S Mihm

Affiliations

Soon will be listed here.

Abstract

Hepatitis C virus (HCV) infection causes acute and often also chronic liver disease. Worldwide, prevalence of infection is estimated to exceed that of human immunodeficiency virus infection fourfold. Because of the lack of appropriate animal models, knowledge of interactions between virus and host is still limited. Assumptions regarding pathogenesis or the activation status of innate antiviral host responses, for instance, derive mainly from clinical observations and from expression analyses of selected genes. To obtain a more objective insight into virus-host interrelationships, we used suppression-subtractive hybridization to compare gene expression in HCV-infected and non-HCV-infected liver tissues samples. Four differentially expressed genes were found: (i) the gamma interferon (IFN-gamma)-inducible chemokine IP-10 gene; (ii) the IFN-alpha/beta-inducible antiviral MxA gene; (iii) the gene encoding IFN-alpha/beta-inducible p44, shown to be associated with ultrastructural cytoplasmic entities within hepatocytes of non-A, non-B hepatitis-infected chimpanzees; and (iv) the gene encoding IFN-alpha/beta/gamma-inducible IFI-56K, a protein recently shown to interact with the eukaryotic translation initiation factor eIF-3. Compared to hepatic gene expression in patients with liver diseases unrelated to viral infections, expression in patients with chronic HCV infection was up to 50-fold higher. While in patients with chronic HBV infection IP-10 was slightly activated as well, the IFN-alpha/beta-regulated genes were not. Revealing a dominance of hepatic interferon-regulated processes in chronic HCV infection, data on the enhanced expression of the IFN-gamma regulated IP-10 support earlier findings and may explain the composition of the hepatic cellular infiltrate. The data on enhanced expression of IFN-alpha/beta inducible genes might be germane to therapeutic considerations.

Citing Articles

During HCV DAA Therapy Plasma Mip1B, IP10, and miRNA Profile Are Distinctly Associated with Subsequent Diagnosis of Hepatocellular Carcinoma: A Pilot Study.

Damjanovska S, Alao H, Zebrowski E, Kowal C, Kostadinova L, Davitkov P Biology (Basel). 2022; 11(9).

PMID: 36138741 PMC: 9495750. DOI: 10.3390/biology11091262.

Interleukin-6-Production Is Responsible for Induction of Hepatic Synthesis of Several Chemokines as Acute-Phase Mediators in Two Animal Models: Possible Significance for Interpretation of Laboratory Changes in Severely Ill Patients.

Malik I, Ramadori G Biology (Basel). 2022; 11(3).

PMID: 35336843 PMC: 8945369. DOI: 10.3390/biology11030470.

Interferon-γ-Inducible Protein 10 (IP-10) Kinetics after Antiretroviral Treatment Initiation in Ethiopian Adults with HIV.

Thorman J, Bjorkman P, Marrone G, Balcha T, Tesfaye F, Abdissa T Microbiol Spectr. 2021; 9(3):e0181021.

PMID: 34908450 PMC: 8672912. DOI: 10.1128/Spectrum.01810-21.

Hepatic Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology.

Huschka H, Mihm S Int J Mol Sci. 2021; 22(15).

PMID: 34360569 PMC: 8345952. DOI: 10.3390/ijms22157803.

Immunomodulation of CXCL10 Secretion by Hepatitis C Virus: Could CXCL10 Be a Prognostic Marker of Chronic Hepatitis C?.

Ferrari S, Fallahi P, Ruffilli I, Elia G, Ragusa F, Paparo S J Immunol Res. 2019; 2019:5878960.

PMID: 31485460 PMC: 6702819. DOI: 10.1155/2019/5878960.

References

Meier V, Mihm S, Ramadori G . MxA gene expression in peripheral blood mononuclear cells from patients infected chronically with hepatitis C virus treated with interferon-alpha. J Med Virol. 2000; 62(3):318-26. View

Guo J, Sen G . Characterization of the interaction between the interferon-induced protein P56 and the Int6 protein encoded by a locus of insertion of the mouse mammary tumor virus. J Virol. 2000; 74(4):1892-9. PMC: 111667. DOI: 10.1128/jvi.74.4.1892-1899.2000. View

Pfeifer U, THOMSSEN R, Legler K, BOTTCHER U, Gerlich W, Weinmann E . Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees. Virchows Arch B Cell Pathol Incl Mol Pathol. 1980; 33(3):233-43. DOI: 10.1007/BF02899184. View

Dugaiczyk A, Law S, Dennison O . Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci U S A. 1982; 79(1):71-5. PMC: 345663. DOI: 10.1073/pnas.79.1.71. View

Chebath J, Merlin G, Metz R, Benech P, Revel M . Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA. Nucleic Acids Res. 1983; 11(5):1213-26. PMC: 325791. DOI: 10.1093/nar/11.5.1213. View

Shimizu Y, Oomura M, Abe K, Uno M, Yamada E, Ono Y . Production of antibody associated with non-A, non-B hepatitis in a chimpanzee lymphoblastoid cell line established by in vitro transformation with Epstein-Barr virus. Proc Natl Acad Sci U S A. 1985; 82(7):2138-42. PMC: 397508. DOI: 10.1073/pnas.82.7.2138. View

Luster A, Unkeless J, Ravetch J . Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985; 315(6021):672-6. DOI: 10.1038/315672a0. View

Hamada H, Reddy P, KAKUNAGA T . Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985; 82(18):6133-7. PMC: 391006. DOI: 10.1073/pnas.82.18.6133. View

Wathelet M, Moutschen S, Defilippi P, Cravador A, Collet M, Huez G . Molecular cloning, full-length sequence and preliminary characterization of a 56-kDa protein induced by human interferons. Eur J Biochem. 1986; 155(1):11-7. DOI: 10.1111/j.1432-1033.1986.tb09452.x. View

10.

Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M . Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989; 244(4902):359-62. DOI: 10.1126/science.2523562. View

11.

Goetschy J, Zeller H, Content J, Horisberger M . Regulation of the interferon-inducible IFI-78K gene, the human equivalent of the murine Mx gene, by interferons, double-stranded RNA, certain cytokines, and viruses. J Virol. 1989; 63(6):2616-22. PMC: 250741. DOI: 10.1128/JVI.63.6.2616-2622.1989. View

12.

Maeda T, Honda Y, Hanawa M, Yamada E, Ono Y, Shikata T . Production of antibodies directed against microtubular aggregates in hepatocytes of chimpanzees with non-A, non-B hepatitis. J Gen Virol. 1989; 70 ( Pt 6):1401-7. DOI: 10.1099/0022-1317-70-6-1401. View

13.

Aebi M, Fah J, Hurt N, Samuel C, Thomis D, Bazzigher L . cDNA structures and regulation of two interferon-induced human Mx proteins. Mol Cell Biol. 1989; 9(11):5062-72. PMC: 363658. DOI: 10.1128/mcb.9.11.5062-5072.1989. View

14.

Honda Y, Kondo J, Maeda T, Yoshiyama Y, Yamada E, Shimizu Y . Isolation and purification of a non-A, non-B hepatitis-associated microtubular aggregates protein. J Gen Virol. 1990; 71 ( Pt 9):1999-2004. DOI: 10.1099/0022-1317-71-9-1999. View

15.

Memet S, BESANCON F, Bourgeade M, THANG M . Direct induction of interferon-gamma- and interferon-alpha/beta-inducible genes by double-stranded RNA. J Interferon Res. 1991; 11(3):131-41. DOI: 10.1089/jir.1991.11.131. View

16.

Taub D, Lloyd A, Conlon K, Wang J, Ortaldo J, Harada A . Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med. 1993; 177(6):1809-14. PMC: 2191047. DOI: 10.1084/jem.177.6.1809. View

17.

Minutello M, Pileri P, Unutmaz D, Censini S, Kuo G, Houghton M . Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J Exp Med. 1993; 178(1):17-25. PMC: 2191080. DOI: 10.1084/jem.178.1.17. View

18.

Sato K, Okamoto H, Aihara S, Hoshi Y, Tanaka T, Mishiro S . Demonstration of sugar moiety on the surface of hepatitis C virions recovered from the circulation of infected humans. Virology. 1993; 196(1):354-7. DOI: 10.1006/viro.1993.1488. View

19.

Jakschies D, Zachoval R, Muller R, Manns M, Nolte K, Hochkeppel H . Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C. Hepatology. 1994; 19(4):857-65. View

20.

Chazouilleres O, Kim M, Combs C, Ferrell L, Bacchetti P, Roberts J . Quantitation of hepatitis C virus RNA in liver transplant recipients. Gastroenterology. 1994; 106(4):994-9. DOI: 10.1016/0016-5085(94)90759-5. View